摘要目的：探讨DNA错配修复（MMR）蛋白免疫组织化学染色筛查微卫星不稳定性（MSI）结直肠癌的敏感度和特异度。方法选取结直肠癌病例255例（常规切片140例，组织芯片115例），免疫组织化学法检测MLH1、MSH2、MSH6、PMS2蛋白表达情况，肿瘤细胞核无着色时计为阴性，着色细胞比例＜5％计为局灶阳性，任何一种蛋白表达阴性即判定肿瘤为MMR蛋白缺失，提示肿瘤为高频MSI。全部病例同时采用PCR－毛细管电泳法直接检测肿瘤MSI状态。结果采用常规切片进行免疫组织化学检测的140例与PCR－毛细管电泳法检测结果的符合率为98．6％（138／140），对MSI肿瘤检测的敏感度为94．9％（37／39），特异度为100．0％（101／101）；与PCR－毛细管电泳法结果不一致的2例均为至少一种蛋白局灶阳性。115例的组织芯片免疫组织化学染色结果可判读率为91．3％（105／115），可判读病例与PCR－毛细管电泳法检测结果的符合率为100．0％（105／105），检测MSI肿瘤的特异度及敏感度均为100．0％；不可判读病例均为至少一种染色内对照细胞核无着色，10例无法判读。结论免疫组织化学法检测4种MMR蛋白表达筛查MSI结直肠癌的方法特异度强，敏感度高，可在日常工作中常规开展。对仅有少数肿瘤细胞核阳性表达的病例应高度可疑MSI肿瘤，需采用PCR－毛细管电泳法检测加以验证。

abstractsObjective To evaluate the sensitivity and specificity of immunohistochemical ( IHC) staining of DNA mismatch repair ( MMR ) protein for the screening of microsatellite instability ( MSI ) colorectal cancer (CRC).Methods A total of 255 CRC cases were studied, including 140 cases of routine paraffin-embedded tissue samples and 115 cases constructed on tissue microarray .Expressions of 4 MMR proteins including MHL1, MSH2, MSH6 and PMS2 were investigated by IHC.Negative protein expression was defined as complete absence of nuclear staining within tumor cells in the presence of positively labeled internal non-neoplastic cells.Focal staining was defined as the presence of staining in <5% of the tumor cells.CRCs showing negative staining for any MMR proteins were interpreted as MMR deficient tumors . PCR-genescan MSI analysis was performed in each case by a five marker panel including Bat 26, Bat25, NR-21, NR-24 and MONO-27.Results Among the 140 CRCs with routine formalin-fixed paraffin embedded tissue sections , concordance rate between IHC and PCR-genescan was 98.6% ( 138/140 ) , the sensitivity&nbsp;and specificity of IHC in detecting MSI tumors were 94.9% ( 37/39 ) and 100.0% ( 101/101 ) , respectively.The 2 disconcordant cases showed focal staining in at least one of the MMR proteins but were confirmed to be MSI-H CRCs by PCR-genescan assay.On tissue microarray, 91.3% (105/115) of the cases had informative results . The concordance rate between IHC and PCR-genescan was 100.0%(105/105).Both the specificity and sensitivity of IHC in detecting MSI tumors on available tissue microarray samples were 100.0%.Ten cases were inclusive due to the presence of negative stains of MMR proteins in both the tumor and internal control cells .Conclusions Detection of 4 MMR proteins expression by IHC is reliable for identifying MSI CRCs and is recommended for routine practice .Tumors with focal MMR protein staining are highly suspected for the presence of MSI-H and PCR-genescan based MSI analysis should be performed to confirm .